Abstract Body: Hypertension (HTN) is a critical health condition impacting nearly 60% of African-American/Black adults (AA), highlighting the urgent need for targeted diagnostic and therapeutic interventions. Despite the known contributions of endothelial dysfunction and oxidative stress and endothelial dysfunction to HTN, the underlying mechanisms remain poorly understood. These mechanisms can lead to significant vascular damage, exacerbating the condition. Traditionally, HTN diagnosis relies on consistent blood pressure (BP) readings under controlled conditions, but these measurements do not directly reveal the drivers of elevated BP. Proteomics offers a powerful tool to investigate HTN at the molecular level and the association of BP with protein levels in this high-risk population.
Our study leveraged BP readings and bottom-up plasma proteomics to evaluate protein levels in an exclusively AA cohort of normotensive and hypertensive participants (N=808) from the Southern Community Cohort Study (SCCS). Due to the high prevalence of HTN among the AA population, we hypothesized to find proteomic patterns that reflect endothelial dysfunction and oxidative stress as BP increases. To test this, high-performance LC-MS/MS data of 58 TMTpro 16-plex plasma batches were acquired on an orbitrap Fusion Lumos instrument, along with a daily pooled-plasma quality control sample to ensure robust and high-confidence data acquisition.
Quantification of over 2600 proteins revealed modest yet discernible expression changes between normotensive and hypertensive proteomes. STRING and Gene Ontology analyses predicted vascular remodeling, endothelial function impairment, and amyloidogenic associations. Noteworthy was the downregulation of E-selectin, a glycoprotein playing a critical role in the adhesion of neutrophils in inflamed endothelium. Additionally, the downregulation of ALDH1A1, a detoxifying agent for aldehydes, suggests increased oxidative stress in hypertensive AAs. Regression analysis of normalized proteins (n=1280) demonstrated significant associations between ALDH1A1 expression and SBP, highlighting it as a potential biomarker candidate for HTN.
In conclusion, our findings support the hypothesis, elucidating molecular mechanisms in African Americans. By correlating proteomic data with BP readings, we advance the understanding of HTN and open avenues for personalized intervention strategies in this high-risk group, essential for the HTN 2025 conference's discourse.